Enterovirus 71 Represses Interleukin Enhancer-Binding Factor 2 Production and Nucleus Translocation to Antagonize ILF2 Antiviral Effects.

Enterovirus 71 (EV71) infection causes hand-foot-mouth disease (HFMD), meningoencephalitis, neonatal sepsis, and even fatal encephalitis in children, thereby presenting a serious risk to public health. It is important to determine the mechanisms underlying the regulation of EV71 infection. In this study, we initially show that the interleukin enhancer-binding factor 2 (ILF2) reduces EV71 50% tissue culture infective dose (TCID50) and attenuates EV71 plaque-formation unit (PFU), thereby repressing EV71 infection. Microarray data analyses show that ILF2 mRNA is reduced upon EV71 infection. Cellular studies indicate that EV71 infection represses ILF2 mRNA expression and protein production in human leukemic monocytes (THP-1) -differentiated macrophages and human rhabdomyosarcoma (RD) cells. In addition, EV71 nonstructural protein 2B interacts with ILF2 in human embryonic kidney (HEK293T) cells. Interestingly, in the presence of EV71 2B, ILF2 is translocated from the nucleus to the cytoplasm, and it colocalizes with 2B in the cytoplasm. Therefore, we present a distinct mechanism by which EV71 antagonizes ILF2-mediated antiviral effects by inhibiting ILF2 expression and promoting ILF2 translocation from the nucleus to the cytoplasm through its 2B protein.

Cullin1 binds and promotes NLRP3 ubiquitination to repress systematic inflammasome activation.

Activation of the NACHT, leucine-rich repeat, and pyrin domains-containing protein 3 (collectively known as NLRP3) inflammasome plays a key role in host immune response, which is the first line of defense against cellular stresses and pathogen infections. However, excessive inflammasome activation damages host cells, and therefore it must be precisely controlled. Here, we discover that Cullin1 (CUL1), a key component of the Skp1-Cullin1-F-box E3 ligase, plays a critical role in controlling the NLRP3 inflammasome. CUL1 represses inflammasome assembly in cultured cells, suppresses NLRP3 function in human monocytic cell line macrophages, and attenuates inflammatory responses in mouse model. Detailed studies demonstrate that CUL1 interacts with NLRP3 and promotes NLRP3 ubiquitination, but not protein degradation, to repress the NLRP3 inflammasome activation. Moreover, upon inflammatory stimuli, including ATP and nigericin treatments, CUL1 disassociates from NLRP3 to release the repression of the NLRP3 inflammasome. Thus, this study reveals a distinct and unique mechanism underlying the control of systematic activation of the NLRP3 inflammasome.-Wan, P., Zhang, Q., Liu, W., Jia, Y., Ai, S., Wang, T., Wang, W., Pan, P., Yang, G., Xiang, Q., Huang, S., Yang, Q., Zhang, W., Liu, F., Tan, Q., Zhang, W., Wu, K., Liu, Y., Wu, J. Cullin1 binds and promotes NLRP3 ubiquitination to repress systematic inflammasome activation.

The use of a second biopsy from the gastric body for the detection of Helicobacter pylori using rapid urease test.

INTRODUCTION: The use of an additional biopsy from the gastric body may help improve the detection of Helicobacter pylori during endoscopy. This study aimed to determine whether such an additional biopsy is necessary in routine rapid urease test (RUT), and whether acid suppression and antibiotic therapy affect RUT results. METHODS: Patients recruited had two gastric mucosal biopsies taken - one from the gastric antrum and the other from the gastric body. Each biopsy was placed into separate RUT kits. Information on previous or current use of proton-pump inhibitors, H2 receptor antagonist, bismuth and antibiotics was obtained. Patients on any of those drugs one week prior to endoscopy were considered to have a positive drug history (PDH). RESULTS: Of the 400 patients recruited, 311 had negative RUTs and 89 had at least one positive RUT. Between the PDH and negative drug history (NDH) groups, there was a significant difference in the distribution of the location of the biopsies that yielded positive RUTs (p = 0.023). The NDH group had a higher proportion of patients who had positive RUTs for both locations, whereas the PDH group had a higher proportion of patients who had positive RUTs for only one location. CONCLUSION: As RUT results are significantly affected by the use of acid suppression and antibiotic therapies, biopsies for RUT should be taken from both the gastric antrum and body to minimise false negative results.

Is hybrid surgery of the cervical spine a good balance between fusion and arthroplasty? Pilot results from a single surgeon series.

PURPOSE: Few studies have investigated the role of hybrid surgery (HS) that incorporates anterior cervical discectomy and fusion (ACDF) and artificial disc replacement (ADR) techniques. To our knowledge, this is the first study that provides a direct comparison of all three groups in terms of intra-operative parameters and outcomes with a minimum follow-up of 2 years. METHODS: Seven consecutive patients who underwent HS were matched with another seven patients who underwent ACDF and ADR based on levels of surgery. Prospective data on demographics, pre-operative and post-operative assessments, complications and functional scores (VAS, NDI, EQ-5D health score and index) were analysed using Mann-Whitney U test. Type I error was set at 5 %. RESULTS: Duration of surgery was significantly shorter for ACDF at 135 min (p = 0.025) compared with HS and ADR. ACDF also had greater blood loss when compared with ADR (p < 0.036). ADR has the shortest duration of hospitalization followed by HS and ACDF (p < 0.031). The HS group returned to work fastest (54 days) when compared with both ACDF (107 days) and ADR (73 days) with statistical significance seen between HS and ACDF (p = 0.035). Cervical range of motion (ROM) and functional scores did not show any significant differences. CONCLUSION: HS is comparable to ACDF and ADR in terms of safety and feasibility. Findings of shorter in-hospital stay and earlier return to work in HS group may be further explored in large, randomised controlled trials.

[Oral mucosa for hypospadias repair: a report of 19 cases].

OBJECTIVE: To investigate the indications and clinical effect of using oral mucosa as the graft in hypospadias repair. METHODS: We performed hypospadias repair using oral mucosa for 19 patients, 10 with the urethral opening at the root of the penis, 7 at the scrotum and 2 at the perineum. Of these patients, 8 had received urethroplasty once, and 6 twice, unsuccessfully, and 7 of them were complicated by penile chordee. The lower lip mucosa was used as the graft for 14 cases, and the buccal mucosa for the other 5. Fifteen cases received autologous oral mucosa onlay for repair, with the new urethra covered by the dartos coat of the dorsal skin. For the other 4 cases, whose urethral plates had been damaged in the previous operations, oral mucosa strips were used to substitute the urethral plates to get the penis straightened, followed by urethroplasty 6 months later. RESULTS: Of the 19 patients, 17 (89.5%) achieved satisfactory results, with a desirable shape of the penis and a vertical slit-like meatus at the tip of the glans. Chordee was corrected in all the patients. No urethral stricture was found during the 3 - 18 months follow-up. Urethral fistula occurred in 2 cases because of infection, but cured by surgical repair 6 months later. CONCLUSION: Using oral mucosa as the graft is an effective surgical option for hypospadias repair.